Current Treatment Options in Oncology

, Volume 14, Issue 2, pp 170–184 | Cite as

Role of Arsenic Trioxide in Acute Promyelocytic Leukemia

  • Harry J. Iland
  • John F. Seymour
Leukemia (JP Dutcher, Section Editor)

Opinion statement

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia that is characterized by distinct clinical, morphological, cytogenetic, and molecular abnormalities. It is associated with a striking risk of early hemorrhagic death due to disseminated intravascular coagulation and hyperfibrinolysis. The prognosis of APL has improved dramatically following the introduction of all-trans retinoic acid (ATRA) and its combination with anthracycline-based chemotherapy during induction and consolidation. Patients with high-risk APL, defined by a white cell count >10 × 109/L at diagnosis, also appear to benefit from the addition of intermediate- or high-dose cytarabine during consolidation. Arsenic trioxide (ATO) has proved to be even more effective than ATRA as a single agent, and is now routinely used for the treatment of the 20%–30% of patients who manifest disease relapse after initial treatment with ATRA and chemotherapy. ATO has a toxicity profile that differs considerably from that of both ATRA and cytotoxic chemotherapy, and accordingly presents its own specific challenges during treatment. Optimizing a strategy for the incorporation of ATO into initial therapy is currently the focus of several cooperative group trials, with an emphasis on minimizing or even eradicating the use of chemotherapy. ATRA plus ATO without chemotherapy appears to be adequate during induction and consolidation for patients with standard-risk APL, but triple therapy that includes limited anthracycline or gemtuzumab ozogamicin (GO) during induction is required for high-risk APL. Uncertainty still exists regarding the minimum amount of chemotherapy and number of consolidation cycles necessary, the optimal scheduling of ATO, and the potential utility of oral ATO administration. Although prolonged oral maintenance therapy is usually included in most current APL treatment protocols, its value remains controversial, and the superior anti-leukemic efficacy of ATO-based therapy may facilitate its elimination in the future.

Keywords

Acute promyelocytic leukemia Arsenic trioxide All-trans-retinoic acid PML-RARA Chemotherapy Induction Consolidation Maintenance Toxicity QTc prolongation Differentiation syndrome Idarubicin Cytarabine Anthracycline Gemtuzumab ozogamicin 

Notes

Disclosure

H.J. Iland: Provided expert testimony to Phebra, received payment for development of educational presentations from Novartis and Elsevier, and had conference accommodation expenses covered by Roche; J.F Seymour: Consultancy for Phebra.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Harry J. Iland
    • 1
    • 2
  • John F. Seymour
    • 3
    • 4
  1. 1.Institute of HaematologyRoyal Prince Alfred HospitalCamperdownAustralia
  2. 2.University of SydneySydneyAustralia
  3. 3.Peter MacCallum Cancer CentreEast MelbourneAustralia
  4. 4.University of MelbourneMelbourneAustralia

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